As the search continues for more effective therapeutic agents, marine microorganisms and invertebrates have emerged as a promising new resource yielding unusual chemical structures with potent biological activities. The vast diversity and relatively unexplored nature of these unique sources of chemical diversity suggests they will continue to be an important source of new drugs. The broad goal of this proposal is to discover marine natural product leads from marine microorganisms. SBIR Phase I aim is to identify extracts with potent antimalarial activity from Magellan's library of marine microorganisms. We seek to isolate structures from microorganisms that will be useful against malaria for which there are few effective drug leads. SBIR Phase II aim will be to identify a high quality lead that will progress towards submission of an IND application. We expect to use a combination of natural products chemistry and anti- malaria screens to discover novel chemical compounds useful as anti-malaria agents. [unreadable] [unreadable] This proposal responds to the key national priority to identify new and effective therapeutics against malaria. Malaria is the most important parasitic disease of man and a major cause of morbidity and mortality in tropical and temperate regions worldwide. It is estimated that over 300 million people become infected with malaria each year, with up to 3 million people dying as a result of the disease. The majority of these deaths occur in children under the age of five and pregnant women in sub- Saharan Africa. [unreadable] [unreadable] [unreadable]